dbSNP rs142192082: CLIP3:p.Arg390Pro (chr19-36018912-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015526.3(CLIP3):c.1169G>C(p.Arg390Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,056 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLIP3
NM_015526.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

CLIP3 (HGNC:24314): (CAP-Gly domain containing linker protein 3) This gene encodes a member of the cytoplasmic linker protein 170 family. Members of this protein family contain a cytoskeleton-associated protein glycine-rich domain and mediate the interaction of microtubules with cellular organelles. The encoded protein plays a role in T cell apoptosis by facilitating the association of tubulin and the lipid raft ganglioside GD3. The encoded protein also functions as a scaffold protein mediating membrane localization of phosphorylated protein kinase B. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

CLIP3 links:

ENSG00000267698 (HGNC:):

ENSG00000267698 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP3	NM_015526.3 link	c.1169G>C	p.Arg390Pro	missense_variant	Exon 9 of 14	ENST00000360535.9	NP_056341.1	Q96DZ5
CLIP3	NM_001199570.2 link	c.1169G>C	p.Arg390Pro	missense_variant	Exon 8 of 13		NP_001186499.1	Q96DZ5
LOC101927572	NR_170987.1 link	n.235-322C>G		intron_variant	Intron 2 of 3
LOC101927572	NR_170988.1 link	n.235-322C>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLIP3	ENST00000360535.9 link	c.1169G>C	p.Arg390Pro	missense_variant	Exon 9 of 14	1	NM_015526.3	ENSP00000353732.3	Q96DZ5
ENSG00000267698	ENST00000586962.1 link	n.229-322C>G		intron_variant	Intron 2 of 3	1
CLIP3	ENST00000593074.5 link	c.1169G>C	p.Arg390Pro	missense_variant	Exon 8 of 13	2		ENSP00000466832.1	Q96DZ5
ENSG00000267698	ENST00000685157.1 link	n.244-322C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461056

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.23

Sift

Benign

0.030

D;.

Sift4G

Uncertain

0.038

D;D

Polyphen

0.93

P;P

Vest4

0.66

MutPred

0.32

Loss of methylation at R390 (P = 0.0125);Loss of methylation at R390 (P = 0.0125);

MVP

0.62

MPC

0.88

ClinPred

0.80

GERP RS

4.9

Varity_R

0.39

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over